TELOMERASE ACTIVITY AND SURVIVAL OF PATIENTS WITH NODE-POSITIVE BREAST-CANCER

Background: Shortening of telomeres (specialized structures at the end s of chromosomes) beyond a certain length may signal a cell to stop di viding and to enter senescence. A ribonucleoprotein enzyme, telomerase , is a key component in maintaining telomere length, Because the major ity of cancers express telomerase but most normal somatic tissues do n ot, we measured the level of telomerase expression in primary breast c ancer specimens for correlation with traditional prognostic indicators and disease outcome. Methods: Telomerase activity was measured in fro zen human breast cancer specimens by use of the Telomeric Repeat Ampli fication Protocol (TRAP) assay, The level of telomerase activity was e xpressed as total product generated (TPG) and was corrected for specim en cellularity by expressing it as a ratio of TPG to the sample's 28S ribosomal RNA content Results: A preliminary study of 150 breast cance r specimens demonstrated that telomerase activity correlated with the fraction of cells in S phase of the cell cycle (r(sp) = .23), Zn a lar ger prognostic study of 398 tumors from patients with lymph node-posit ive breast cancer, telomerase expression correlated with S-phase fract ion, progesterone receptor level, DNA ploidy, and lymph node status. A fter correcting for sample cellularity, increasing TPG levels were ass ociated with decreased disease-free survival (P = .041) and overall su rvival (P = .009) of the patients, The telomerase activity level remai ned strongly predictive of death (P = .027) and marginally predictive of disease recurrence (P = .08) after adjustment for other prognostic factors, All P values are two-sided, Conclusions: Telomerase activity in human breast cancers is associated with a more aggressive tumor phe notype in patients.